Risk as a Driver for Innovation

The Space Life Sciences directorate (SLSD) and Human Research Program (HRP) at NASA Johnson Space Center has implemented a system for managing human systems risks. These risks are defined as the health and performance risks posed to crew during and after spaceflight. Identification and evaluation of these risks has led to the identification of gaps in knowledge about the risks as well as gaps in technology needed to mitigate them. Traditional routes of closing technology gaps have, in some cases, proven to be too slow when a solution was required quickly. Therefore, certain gaps were used to drive the development of "challenges" for the scientific community. Partnering with open innovation service providers such as InnoCentive and Yet2.com, SLSD and HRP have decreased the amount of time from identification of a need to the evaluation of a solution. Although not all proposed solutions will result in a risk mitigation strategy or tool, the process has allowed faster evaluation of proposed solutions providing the researcher the ability to move to another possible solution if the first does not sufficiently address the problem. Moreover, this process engages the community outside of NASA and broadens the population from which to draw solutions. In the traditional grant funding structure, only those in the specific field will apply for the grant. However, using open innovation, solutions can come from individuals in many different fields. This can expand the general view of a field (way of thinking within a field) and the application of solutions form new fields while providing a pathway for the acquisition of novel solutions or refinements of current mitigations. Identification of the human systems risks has helped drive the development and evaluation of innovative solutions as well as engaging a broader scientific audience in working with NASA

Agribusiness Sheep Updates - 2004 - Part 1

Proceedings of the Agribusiness Sheep Updates - 2004 Forward Dr Mark Dolling Manager, Sheep Industries and Pasture, Department of Agriculture Western Australia Keynotes Australian Wool Innovation Limited DR LEN STEPHENS AUSTRALIAN WOOL INNOVATION LIMITED (AWI) Commercialisation of Sheepmeat Eating Quality Outcomes, David Thomason, General Manger Marketing Meat & livestock Australia Limited PLENARY The Fitness of the Future Merino, Norm Adams and Shimin Liu, CSIRO Livestock Industries Ovine Johne’s Disease – Managing the Disease, Managing the Issues, PETER BUCKMAN, CHIEF VETERINARY OFFICER, DEPARTMENT OF AGRICULTURE WESTERN AUSTRALIA Animal Welfare – Changes in Latitudes Changes in Attitudes, Michael Paton and Dianne Evans, Department of Agriculture Western Australian. Live Sheep Exports, JOHN EDWARDS. CHAIRMAN, WESTERN AUSTRALIAN LIVE SHEEP EXPORTERS ASSOCIATION MeCustomising to the Needs of the Customer – Insights from the New Zealand Merino Experience, DR SCOTT CHAMPION, RESEARCH, DEVELOPMENT AND PRODUCT INNOVATION MANAGER, THE NEW ZEALAND MERINO COMPANY LIMITED Agribusiness Sheep Updates Conference -Economic and Financial Market Update Alan Langford, Economist, BankWest Concurrent sessions - Meeting the Market Breeding Wool to Address Consumer Requirements in Fabrics A.C. SCHLINK CSIRO Livestock Industries, J.C. GREEFF AND M. E. LADYMAN Department of Agriculture Western Australia Fibre Contribution to Retail Demand for Knitwear Melanie LadymanA and John StantonAB ADepartment of Agriculture Western Australia and BCurtin University of Technology Sustainable Merino, is this the Future for Merino? Stuart Adams, iZWool International P/L Meeting lamb Market Specs from Crossbred Ewes Dr. Neal Fogarty, NSW Agriculture and the Australian Sheep Industry CRC Use of Serial Body Weight Measurements in Prime Lamb Finishing Systems Matthew Kelly, CSIRO Livestock Industries, James Skerritt, Ian McFarland Department of Agriculture Western Australia, Australian Sheep Industry CR

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.Methods: We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T&gt;G and c.3113G&gt;A, CHEK2c.349A&gt;G, c.538C&gt;T, c.715G&gt;A, c.1036C&gt;T, c.1312G&gt;T, and c.1343T&gt;G and ATM c.7271T&gt;G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.Results: For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10−5), PALB2 c.3113G&gt;A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10−8) and ATM c.7271T&gt;G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A&gt;G OR 2.26 (95% CI 1.29 to 3.95), c.1036C&gt;T OR 5.06 (95% CI 1.09 to 23.5) and c.538C&gt;T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T&gt;G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G&gt;T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.Conclusions: This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.</p

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

HETEROSIS AND GENETIC PARAMETERS FOR REPRODUCTION IN SHEEP

Lamb production, including the components of fertility, litter size, survival and lamb growth, of first cross, and F(,1), F(,2) and F(,3) generation ewes of two maternal composite lines, as well as the parental purebreeds, was investigated to determine levels of heterosis and seasonal effects. The lines were 1/2 Finnsheep 1/4 Rambouillet 1/4 Dorset, joined in an 8-monthly lambing system, and 1/2 Finnsheep 1/4 Suffolk 1/4 Targhee joined in an annual lambing system. Heritability, repeatability and phenotypic and genetic correlations for the various measures of reproduction and lamb production and their components were estimated. Age at puberty and pubertal ovulation rate also were investigated as indirect selection criteria. The data comprised 4219 ewes, which represented 412 known sires, with a total of 10959 joining records. Reproductive performance varied greatly between seasons. Fertility (ewes lambing per ewe joined) over all breed types was .57, .72 and .27, and litter size 1.9, 1.8 and 1.6 for January, May and September lambings for 1976 to 1979 inclusive. April lambings, which only occurred in 1978 and 1979, had higher fertility and litter size than the other three seasons. Consequently ewe reproduction traits were standardised across seasons and years, and adjusted to a three-year-old ewe basis for calculation of heterosis effects and genetic parameters. Retained heterosis was about 40 percent for weight of lamb weaned per ewe joined, 20 percent for fertility, 15 to 20 percent for survival, but near zero for litter size and mean lamb weaning weight. Paternal half-sib heritability estimates of composite and component production traits were low and ranged from .02 to .11. Estimates for the mean of repeated ewe records were higher and ranged from .10 to.16. Daughter-dam regression estimates were similar

Vms1p is a release factor for the ribosome-associated quality control complex.

Eukaryotic cells employ the ribosome-associated quality control complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, Rqc1p, and Rqc2p. Upon ribosome stalling and splitting, the RQC assembles on the 60S species containing unreleased peptidyl-tRNA (60S:peptidyl-tRNA). Ltn1p and Rqc1p facilitate ubiquitination of the incomplete nascent chain, marking it for degradation. Rqc2p stabilizes Ltn1p on the 60S and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with carboxy-terminal alanine and threonine extensions (CAT tails). By mobilizing the nascent chain, CAT tailing can expose lysine residues that are hidden in the exit tunnel, thereby supporting efficient ubiquitination. If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains can aggregate in the cytosol or within organelles like mitochondria. Here we identify Vms1p as a tRNA hydrolase that releases stalled polypeptides engaged by the RQC